Cell-type-specific mechanoadaptation to sustained hydrostatic pressure and flow in glioblastoma cells and astrocytes

Mechanical forces are increasingly recognized as regulators of cellular behavior, yet their impact on glioblastoma cells and astrocytes remains incompletely understood. Here, we investigated the effects of fluid flow and hydrostatic pressure (HP) on human glioblastoma U87-MG cells and immortalized human astrocytes (IM-HAs). HP was associated with a proliferative response in U87-MG cells, reflected by an increased cell number, together with changes in WST-1 metabolic activity and expression of cell cycle regulators, including cyclin D, cyclin E, and MDM2, without altering p21 or p53 levels.

HP was associated with an increased EGFR immunofluorescence signal intensity, normalized to cell number, and altered transcript abundance of genes related to AKT–mTOR and NF-κB signaling, redox regulation, and the mechanosensitive channel TRPV4 in U87-MG cells. Proteomic analysis further revealed pressure-associated changes in metabolic, redox, extracellular matrix, and cytoskeletal processes. In contrast, IM-HAs exhibited limited proliferative responses, but both mechanical stimuli induced morphological remodeling, astrocyte reactivity-associated gene expression, and redox-associated changes, with HP eliciting stronger shifts.

These findings demonstrate that U87-MG cells and IM-HAs exhibit different responses to mechanical stimuli, highlighting distinct proliferative and astrocyte reactivity-associated response patterns. This work was supported by the Marie Skłodowska-Curie Actions (MSCA) Doctoral Network “Theratools—Research training in technological development of scientific tools for cancer research” (GA 101073404). Smart Bio-Interfaces, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025, Pontedera, Italy Kamil Ziaja, Attilio Marino & Gianni Ciofani The Biorobotics Institute, Scuola Superiore Sant’Anna, Viale Rinaldo Piaggio 34, 56025, Pontedera, Italy Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, Rua de Calouste Gulbenkian 1, 3810-074, Aveiro, Portugal Core Facilities-Clinical Proteomics and Metabolomics, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147, Genova, Italy Correspondence to Kamil Ziaja, Attilio Marino or Gianni Ciofani.

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To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Ziaja, K., Marino, A., Petretto, A. et al. Cell-type-specific mechanoadaptation to sustained hydrostatic pressure and flow in glioblastoma cells and astrocytes.